Adiponectin mediates anti-diabetic effects via increasing hepatic insulin sensitivity and direct metabolic effects. In the present study, we conducted a comprehensive and unbiased metabolomic profiling of liver tissue from AdKO (adiponectin-knockout) mice, with and without adiponectin supplementation, fed on an HFD (high-fat diet) to derive insight into the mechanisms and consequences of insulin resistance. Hepatic lipid accumulation and insulin resistance induced by the HFD were reduced by adiponectin. The HFD significantly altered levels of 147 metabolites, and bioinformatic analysis indicated that one of the most striking changes was the profile of increased lysophospholipids. These changes were largely corrected by adiponectin, at least in part via direct regulation of PLA2 (phospholipase A2) as palmitate-induced PLA2 activation was attenuated by adiponectin in primary hepatocytes. Notable decreases in several glycerolipids after the HFD were reversed by adiponectin, which also corrected elevations in several diacyglycerol and ceramide species. Our data also indicate that stimulation of ω-oxidation of fatty acids by the HFD is enhanced by adiponectin. In conclusion, this metabolomic profiling approach in AdKO mice identified important targets of adiponectin action, including PLA2, to regulate lysophospholipid metabolism and ω-oxidation of fatty acids.
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Research Article|
June 19 2015
Metabolomic profiling in liver of adiponectin-knockout mice uncovers lysophospholipid metabolism as an important target of adiponectin action
Ying Liu;
Ying Liu
*Department of Biology, York University, Toronto, Ontario, Canada, M3J 1P3
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Sanjana Sen;
Sanjana Sen
*Department of Biology, York University, Toronto, Ontario, Canada, M3J 1P3
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Sivaporn Wannaiampikul;
Sivaporn Wannaiampikul
*Department of Biology, York University, Toronto, Ontario, Canada, M3J 1P3
†Department of Tropical Nutrition and Food Science, Mahidol University, Bangkok 10400, Thailand
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Rengasamy Palanivel;
Rengasamy Palanivel
*Department of Biology, York University, Toronto, Ontario, Canada, M3J 1P3
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Ruby L. C. Hoo;
Ruby L. C. Hoo
‡State Key Laboratory of Pharmaceutical Biotechnology, and Department of Medicine, University of Hong Kong, Pokfulam, Hong Kong
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Ruth Isserlin;
Ruth Isserlin
§The Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario, Canada, M5S 3E1
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Gary D. Bader;
Gary D. Bader
§The Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario, Canada, M5S 3E1
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Rungsunn Tungtrongchitr;
Rungsunn Tungtrongchitr
†Department of Tropical Nutrition and Food Science, Mahidol University, Bangkok 10400, Thailand
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Yves Deshaies;
Yves Deshaies
║Department of Medicine and Québec Heart & Lung Institute Research Centre, Université Laval, Québec City, Québec, Canada, G1V 4G5
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Aimin Xu;
Aimin Xu
‡State Key Laboratory of Pharmaceutical Biotechnology, and Department of Medicine, University of Hong Kong, Pokfulam, Hong Kong
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Gary Sweeney
Gary Sweeney
1
*Department of Biology, York University, Toronto, Ontario, Canada, M3J 1P3
1To whom correspondence should be addressed (email gsweeney@yorku.ca).
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Publisher: Portland Press Ltd
Received:
December 01 2014
Revision Received:
April 20 2015
Accepted:
April 27 2015
Accepted Manuscript online:
April 27 2015
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2015 Authors; published by Portland Press Limited
2015
Biochem J (2015) 469 (1): 71–82.
Article history
Received:
December 01 2014
Revision Received:
April 20 2015
Accepted:
April 27 2015
Accepted Manuscript online:
April 27 2015
Citation
Ying Liu, Sanjana Sen, Sivaporn Wannaiampikul, Rengasamy Palanivel, Ruby L. C. Hoo, Ruth Isserlin, Gary D. Bader, Rungsunn Tungtrongchitr, Yves Deshaies, Aimin Xu, Gary Sweeney; Metabolomic profiling in liver of adiponectin-knockout mice uncovers lysophospholipid metabolism as an important target of adiponectin action. Biochem J 1 July 2015; 469 (1): 71–82. doi: https://doi.org/10.1042/BJ20141455
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